Treponema pallidum induces intrinsic apoptosis in hepatocytes by facilitating mitochondrial ROS accumulation to promote cardiolipin peroxidation.

Liver involvement in the course of syphilis can be observed, and hepatocyte apoptosis is a common mechanism of liver damage, the liver's high metabolic activity and the abundance of mitochondria in hepatocytes suggest that mitochondria-mediated intrinsic apoptosis warrants comprehensive investigation in the course of syphilis. After hepatocytes THLE-2 cells were incubated with Treponema pallidum (T. pallidum), we analyzed intrinsic apoptosis alongside key mitochondrial functional parameters. Mitochondrial cardiolipin peroxidation in THLE-2 cells was measured concurrently. In THLE-2 cells, T. pallidum treatment induced a dose-dependent increase in apoptosis rates (P < 0.01), correlated with the upregulation of key apoptosis-related proteins including Bax/Bcl-2 ratio (P < 0.05), Cyt-c (P < 0.01), Caspase-9 (P < 0.001), Caspase-3 (P < 0.05) and Cleaved-Caspase-3 (P < 0.001). This was accompanied by dose-dependent mitochondrial dysfunction, characterized by loss of mitochondrial membrane potential (P < 0.001), reduced adenosine triphosphate levels (P < 0.001), enhanced mitochondrial permeability transition pore opening (P < 0.01), ROS accumulation (P < 0.01), as well as elevated levels of oxidized cardiolipin (P < 0.05). Furthermore, targeted ROS inhibition reversed the mitochondrial damage, cardiolipin peroxidation, and intrinsic apoptosis (P < 0.05). Treponema pallidum could induces intrinsic apoptosis in hepatocytes. This process is driven by mitochondrial dysfunction and a consequent ROS accumulation, which triggers pivotal cardiolipin peroxidation. It provide valuable insights for further understanding the pathogenic mechanisms of syphilitic hepatitis.